Dysregulation of monocyte differentiation in asthmatic subjects is reversed by IL-10

Purpose: The chronic peribronchial inflammation in asthma is associated with an imbalance within the functionally distinct macrophage populations of the endobronchial wall. This may result from aberrant regulation of the emergence of macrophage subsets from recruited monocytes. Methods: Monocytes from 14 normal individuals and 14 atopic asthmatics were grown in culture for 7 days in the presence or absence of T cell cytokines, added on day 5. Double immunofluorescence studies were performed on cytospins of the differentiated macrophages using the monoclonal antibodies RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. HLADR expression was quantified using the monoclonal antibody RFDR1. Results: With no cytokine addition a similar proportion of monocytes from asthmatic and normal subjects differentiated into macrophages expressing an antigen presenting cell phenotype (RFD1+ve RFD7-ve); 52% and 53% respectively. The maturation of macrophages with a suppressive phenotype (RFD1+ve RFD7+ve) at day 7 was however reduced in the asthmatic samples (18%) compared to normals (25%). The addition of IL-10 to these cultures increased the differentiation of suppressive cells in both asthmatics and normal subjects. However the increase in asthmatic subjects following IL-10 addition was significantly greater (94% increase) compared to that in normal subjects (32% increase, p<0.01), thus redressing the balance seen originally. IL-10 addition also reduced the expression of HLADR on the cells from both samples. Conclusions: These results suggest that a fundamental problem exists in the differentiation of monocytes in asthmatic subjects and leads us to hypothesise that altered homeostasis in asthma with increased proportions of antigen presenting macrophages and reduced proportions of suppressive cells may result from dysfunction in IL-10/macrophage interaction. Clinical implications: Therapeutic approaches to regulate IL-10 production and interaction with macrophages may offer a novel approach to asthma management.